Parkinson's disease (PD) is a prevalent age-related neurodegenerative disease associated with the aggregation of the neuronal protein α-synuclein (α-syn) into β-sheet-rich fibrils, called amyloid. Natively, α-syn is an intrinsically disordered protein, and it is thought conformational changes in α-syn are linked to its pathogenicity. Thus, the ability to determine conformational changes of α-syn from soluble, unstructured monomers to β-sheet-rich aggregates is critical for understanding the role of amyloid fibrils in disease progression. However, collecting detailed structural information on these protein aggregates is inherently difficult due to their insoluble, non-crystalline, and polymorphic nature. In this work, I show that Raman microspectorscopy is well-suited for overcoming these challenges and characterizing molecular differences in α-syn fibrils in vitro that are not apparent through other standard amyloid characterization methods. Further, using biosynthetic vibrational probes, I demonstrate the observation of isotopic-shifts and alkyne Raman signatures for α-syn amyloid fibrils in cellular environments. My results indicate that Raman microspectroscopy is a powerful method for structurally characterizing amyloid formation in cellular systems and will reveal molecular insights that are not accessible through other microscopies.
Jessica is currently a postdoctoral fellow in the lab of Dr. Jennifer Lee at the National Institutes of Health, where she develops new experimental methods for studying amyloid formation. Jessica received her Ph.D. under the guidance of Dr. Julie Biteen at the University of Michigan, where she studied plasmon-enhanced fluorescent protein emission using single-molecule techniques. When not in the lab, she enjoys drinking coffee and hiking with her husband, Dan, and her dog, Sophia.